PDB ID Research Articles

Bioassay‐Guided Extraction and Isolation of Natural Herbicides from Dried Zanthoxylum limonella Alston Fruits

AbstractWeeds are problematic plant species around the world. Various strategies exist for controlling weeds, but chemical treatment remains the preferred method, particularly when using natural substances. In this research, a crude aqueous‐methanol extract from dried Zanthoxylum limonella fruits was acid‐base partitioned into four fractions: neutral extract (NE), acid extract (AE), basic extract (BE), and aqueous extract (AQ). These fractions were further separated into seventeen subfractions: NEF1 to NEF7, AEF1 to AEF5, and BEF1 to BEF5, which were then tested for herbicidal activity against the growth of Chinese amaranth (Amaranthus tricolor) and barnyard grass (Echinochloa crus‐galli). Active subfractions were isolated via column chromatography and identified using spectroscopic methods, yielding seven active compounds: xanthoxyline (1), tambulin (2), atanine (3), prudomestin (4), skimmianine (5), p‐methoxybenzoic acid (6), and methyl caffeate (7). Compounds 2–7 had not been previously reported in Z. limonella. Xanthoxyline (1) was identified as the most potent botanical herbicide, fully inhibiting seed germination of Chinese amaranth and barnyard grass. This compound also decreased seed imbibition and α‐amylase activity in both species. Molecular docking studies on the α‐amylase enzyme (PDB ID: 1BG9) revealed that the aromatic, hydroxy, and carbonyl groups of xanthoxyline (1) interact with the enzyme's active sites.

High Throughput Screening and Molecular Docking Analysis on DNA Polymerase (Pol) Β Cancer Variant K289M

DNA polymerase (pol) β plays a critical role in DNA repair mechanisms, and mutations in this enzyme have been implicated in various cancers. Because it may play a role in oncogenesis by altering the fidelity of DNA synthesis, the K289M variation of pol β is particularly interesting. This study uses Python molecular graphic, Cavity based docking, SwissDock, Structure validation server among other computational tools to undertake high-throughput screening and molecular docking investigations of DNA pol β cancer variant K289M (PDB ID: 6NKR). Ligands such as Boceprevir, Nirmatrelvir, Ritonavir, Carmofur, and Lopinavir were docked to identify potential inhibitors targeting this variant. Structural validation using the SAVES server and topology analysis using PDBSum helped assess the quality of the protein structure. Our results highlight several binding pockets with strong ligand affinities, suggesting potential therapeutic interventions for targeting pol β K289M in cancer.

Benzofuran-chalcone derivatives as VEGFR-2 inhibitors: synthesis and anticancer evaluation.

The discovery and development of efficient VEGFR-2 inhibitors has become a research hotspot in cancer treatment. In this work, a series of new benzofuran-based chalcone derivatives have been prepared, and in vitro anticancer activities have been evaluated. The results revealed that derivatives showed selective cytotoxic activity against HCC1806, Hela and A549 cell lines, especially 5c exhibited excellent inhibitory effect on VEFGR-2 (IC50 = 1.07 nM). The molecular docking study indicated that 5c had an obvious binding site with the target VEGFR-2 (PDB ID: 4BSK). Therefore, the benzofuran-based chalcone derivatives could be potent VEGFR-2 inhibitors.

Biogenic synthesis of silver nanoparticles from Hylocereus undatus peel waste: exploring EGFR inhibition for targeted therapy of cervical and breast carcinomas

Abstract Background Cancer is one of the leading causes of death worldwide, with breast and cervical cancers being the most common among women. Over 100,000 new cases of breast cancer and 510,000 new cases of cervical cancer are diagnosed annually. This study aimed to develop and evaluate an eco-friendly, low-cost method to synthesize silver nanoparticles using Hylocereus undatus (dragon fruit) peel extract for their anticancer activity. Results Silver nanoparticles loaded with Hylocereus undatus fruit peel extract were successfully developed by a green synthesis technique and were optimized by UV–vis spectroscopy. The nanoparticles had an average size of 71.66 nm, a polydispersity index of 0.3754, and a zeta potential of − 38.52, with a spherical shape and 79.5% silver content. Their maximum absorbance was at 448 nm. Further, in vitro anticancer activity via MTT (3-(4, 5-dimethylthiazolyl-2)-2, 5-diphenyltetrazolium bromide) assay was evaluated and the synthesized nanoparticles displayed IC50 values at 23.51 µg/ml and 23.66 µg/ml against Hela and MDA MB 231 cell lines, respectively. Cytocompatibility studies showed high cell viability (≥ 95%) in L929 mouse fibroblast cells, indicating low toxicity. In silico analyses, including network pharmacology and molecular docking, identified kaempferol and quercetin as key anticancer compounds, with epidermal growth factor receptor (EGFR) (PDB ID: IM17) being the most significant protein target. Docking studies performed by using the Glide module of Schrodinger’s software displayed that kaempferol and quercetin had higher binding affinities for EGFR as compared to the standard drug erlotinib, with MET 769 being a crucial binding site. Conclusion Thus, the outcomes suggest that synthesized silver nanoparticles loaded with Hylocereus undatus fruit peel extract could be a potential and promising drug carrier aiding in cancer treatment.

Anticancer, antimicrobial, insecticidal and molecular docking of sarcotrocheliol and cholesterol from the marine soft coral Sarcophyton Trocheliophorum.

The anticancer, antimicrobial, and insecticidal activities of sarcotrocheliol (1) and cholesterol (2) obtained from the soft coral Sarcophyton trocheliophorum (S. trocheliophorum) were intensively studied. According to this study, both compounds 1 and 2 showed potential cytotoxicity towards the human colorectal carcinomaHCT-116 (IC50 10.4, 11.8µg/mL) and human liver carcinoma HepG2 cell lines (IC50 8.8, 12.0µg/mL), respectively. Compounds 1 and 2 were evaluated as potential inhibitors of caspase-3, a member of the cysteine protease family, which is considered a key enzyme in inducing cell apoptosis. Results showed that compounds 1 and 2 have induced apoptosis via up-regulation of caspase-3. Sarcotrocheliol (1) displayed antimicrobial activity against P. aeruginosa (15mm), B. subtilis (15mm), M. luteus (14mm) and C. albicans (15mm), with a MIC of 1.5µg/mL against the reported test microorganisms. On the other hand, cholesterol (2) showed less activity towards P. aeruginosa (10mm), B. subtilis (14mm), S. aureus (12mm) and C. albicans (10mm) with MICs of 3.0, 1.5, 1.5 and 3.0µg/mL against the tested microorganisms, respectively. Larvicidal activity revealed that compounds 1 and 2 induced remarkable toxicity against the third instar larvae of the mosquito, Culex pipiens even at concentration of 2 ppm. Adulticidal activity data showed that tested compounds are distinctly potent toxicants against the housefly, Musca domestica adult females. Overall, compound 2induced much more insecticidal activity than 1, and M. domestica adult females were more sensitive to tested compounds than C. pipiens larvae. Computationally, Density Functional Theory (DFT) analyses revealed that compound 2 had a higher dipole moment and lower band gap energy when compared to compound 1. So, compounds 2 is chemically more reactive and less stable than compound 1. According to the molecular docking study against PDB IDs: 3KJF, 5UHF and 1ACJ, compounds 1 and 2 demonstrated their activity mode as anticancer, antimicrobial, and insecticidal agents. The compounds exerted many interactions and showed high binding to the proteins, recognizing their potential as drug candidates with broad bioactivities.

Isolation, Identification, Phytochemical Characterization, and In Vitro Anti-Inflammatory Property of an Endophytic Trametes Versicolor CL-1 Isolated from Rosa Roxburghii.

This study explores the anti-inflammatory potential of an endophytic fungus, Trametes versicolor CL-1, isolated from the fruit tissues of Rosa roxburghii. Morphological and molecular analyses confirmed the identity of CL-1. An ethyl acetate extract (CL-E) from its fermentation broth was subjected to UPLC-HRMS and GNPS molecular networking. The analysis revealed a diverse array of secondary metabolites, including 11 terpenes, 7 flavonoids, 10 cinnamic acid derivatives, 6 oligopeptides, and 9 fatty acids, as verified by LC-MS/MS. Notably, CL-E exhibited significant in vitro anti-inflammatory activity in RAW264.7 cells. Furthermore, molecular docking studies predicted favorable binding interactions of key compounds 1 within CL-E with the NLRP3 inflammasome (PDB ID: 6NPY). These findings suggest T. versicolor CL-1 as a promising source of natural anti-inflammatory agents and unveil R. roxburghii as a potential reservoir for discovering novel bioactive metabolites.

Unlocking the Immunomodulatory Potential of Rosmarinic Acid Isolated from Punica granatum L. using Bioactivity-Guided Approach: In Silico, In Vitro, and In Vivo Approaches.

Punica granatum L. is well-known for its multifaceted therapeutic potential, including anti-inflammatory and immunomodulatory activities. This study aimed to characterize an immunomodulatory compound isolated from Punica granatum L. using a bioactivity-guided approach. Chromatographic techniques were adopted for isolation and purification of secondary metabolites. In silico, in vitro, and in vivo methods were performed to characterize the therapeutic potential of the isolated compound. Using preparative thin-layer chromatography, rosmarinic acid was isolated from F4 (column chromatography product obtained from a butanolic fraction of the extract). The impact of rosmarinic acid was assessed in rats using the neutrophil adhesion test, DTH response, and phagocytic index. In immunized rats, rosmarinic acid demonstrated significant immunomodulatory potential. Computational experiments, like molecular docking and molecular dynamics, were also conducted against two targeted receptors, Cereblon (PDB ID: 8AOQ) and human CD22 (PDB ID: 5VKM). Computational studies suggested that an increase in phagocytic index by rosmarinic acid could be attributed to inhibiting Cereblon and CD22. Pharmacokinetics and toxicity prediction also suggested the drug-likeness of rosmarinic acid. Rosmarinic acid is a potential candidate, but extensive research needs to be done to translate this molecule from bench to bedside.

Repurposing of Statins Against Superficial Fungal Infections

In a few decades fungal infections will become a major worldwide health concern. Research reveal that the fungal strain becomes resistant to current medications in cases of HIV infections, corona infections and environmental factors particularly in people with impaired immune systems. The amount of organ transplants and medication used for therapy all have contributed to an increase in the immunocompromised population. The fungal infections are becoming a more significant cause of mortality and morbidity. An estimated 1.5 million fatal consequences are caused by fungal pathogens annually. In a few decades, fungal infections will become a major worldwide health concern, so that unprecedented rates of fungal resistance to currently available antifungal medicines has been observed.The drug repurposing approaches lowers costs and time by investigating previously approved medicines with known safety and pharmacokinetics toxicity profile for novel therapeutic effects.The HMG – CoA reductase inhibitors drugs statins shows antifungal properties against tinea spp. group of common fungus that causes superficial infections. We have evaluated statins for their antifungal potential by insilico studies & Invitro studies & validate results with standard drugs itraconazole & ketoconazole.The docking studies shows highest binding energy shown by atorvastatin among all statin were used for docking studies pravastatin , atorvastatin, simavastatin ,fluvastatin & rosuvastatin . against fungal protein (PDB ID:5V5Z) & human protein (PDB ID: 3LD6) was found to be -13.52 &13.4 kcal/mole .The invitro studies shows MIC values for atorvastatin against Trichophyton rubrum , Microsporum canis & Epidermatophyton flocossum fungal strains found between 125 μg/ml to 150 125 μg/ml where as for standard drugs was found between 12.5 μg/ml to 25 μg/ml. Following insilico & invitro research atorvastatin determined and may be used for the treatment of fungal infections.

In-silico Screening and Synthesis of Benzo[c]Pyridazines Targeting N-Methyl D-Aspartate Glutamate Receptor for the Treatment of Seizures.

This study focuses on synthesizing novel benzopyridazine compounds with an evaluation of their anti-epileptic activity by in-silico screening and MES test. The compounds were synthesized under controlled conditions by the reaction of the substituted anilines with sodium nitrite, followed by the reaction with cyanoacetamide, substituted urea, ethanol, and water. The final compounds (5a-d; 6a-d) were tested for antiepileptic activity by in-silico screening targeting N-Methyl D-Aspartate glutamate receptor (PDB ID:5IPV). The screened compounds are also evaluated by in vivo test (MES) by taking phenytoin as a standard drug. The results of the whole study were satisfactory with the yield of the compounds in the range of 88 % to 96 %. The results of in- silico, screening showed that compounds 6a and 6c have far more binding energy compared with standard phenytoin (6a -7.5 Kcal/mol. ; 6c -7.6 Kcal/mol. and Phenytoin -6.5 Kcal/mol.). The TD50 values of synthesized compounds (6a-6d) are observed to be significantly higher than those of standard phenytoin. The PI values of several synthetic compounds (6a and 6c) were found to be higher (55.8 % and 58.0 %) than the current antiepileptic medicine phenytoin (55.6 %), demonstrating the synthesized compound's safety potential.

Crystal structure, Hirshfeld surface analysis, DFT and molecular docking studies of ethyl 5-amino-2-bromoisonicotinate

In the title compound, C8H9BrN2O2, the C—O—C—C torsion angle between isonicotine and the ethyl group is 180.0 (2)°. Intramolecular N—H...O and C—H...O interactions consolidate the molecular structure. In the crystal, N—H...N interaction form S(5) zigzag chains along [010]. The most significant contributions to the Hirshfeld surface arise from H...H (33.2%), Br...H/H...Br (20.9%), O...H/H...O (11.2%), C...H/H...C (11.1%) and N...H/H...N (10%) contacts. The topology of the three-dimensional energy frameworks was generated using the B3LYP/6–31 G(d,p) model to calculate the total interaction energy. The net interaction energies for the title compound are E ele = 59.2 kJ mol−1, E pol = 15.5 kJ mol−1, E dis = 140.3 kJ mol−1 and E rep = 107.2 kJ mol−1 with a total interaction energy E tot of 128.8 kJ mol−1. The molecular structure was optimized by density functional theory (DFT) at the B3LYP/6–311+G(d,p) level and the theoretical and experimentally obtained parameters were compared. The frontier molecular orbitals HOMO and LUMO were generated, giving an energy gap ΔE of 4.0931 eV. The MEP was generated to identify active sites in the molecule and molecular docking studies carried out with the title compound (ligand) and the covid-19 main protease PDB ID: 6LU7, revealing a moderate binding affinity of −5.4 kcal mol−1.

Biochemical characterization and structure prediction of the Cerrado soil CRB2(1) metagenomic dioxygenase

Dioxygenases are enzymes involved in the conversion of polyconic aromatic hydroxycarbons (PAHs), attracting significant biotechnological interest for the conversion of recalcitrant organic compounds. Furthermore, few studies show that dioxygenases can take on the function of resistance genes in clones. This enzymatic versatility opens up new opportunities for elucidating the mechanisms of microbial resistance, as well as its biotechnological application. In this work, a Cerrado soil dioxygenase named CRB2(1) was biochemically characterized. The enzyme was shown to have optimal activity at pH 7; a temperature of 30 °C; and using iron ions as a cofactor for substrate cleavage. The kinetic catalytic parameters of CRB2(1) were Vmax = 0.02281 µM/min and KM = 97.6. Its predicted three-dimensional structure obtained using the Modeller software v9.22 based on the crystal structure of gentisate 1,2-dioxygenase from Silicibacter pomeroyi (GDOsp) (PDB ID 3BU7, resolution 2.80 Å, residues 17–374) revealed substrate binding to the cupin domain, where the active site is located. The analyzed substrates interact directly with the iron ion, coordinated by three histidine residues. Changing the iron ion charge modifies the binding between the active site and the substrates. Currently, there is a demand for enzymes that have biotechnological activities of interest. Metagenomics allows analyzing the biotechnological potential of several organisms at the same time, based on sequence and functional activity analyses.

Inhibitory Potency of Chlorogenic Acid from Apple Cider Vinegar Against Alzheimer’s Disease: Molecular Docking and Dynamics Validation

Objective The primary cause of memory loss is Alzheimer’s disease (AD). Recent studies have shown that natural compounds like apple cider vinegar (ACV) have anti-Alzheimer’s capabilities. Essential components of ACV, such as gallic acid and chlorogenic acid, may be in charge of the drug’s pharmacological effects. Methods Using molecular docking and dynamics (MD), the current work looks at the aspect of ACV that protects against AD. To study the conformational relationships and interaction mechanisms between two biological molecules (such as interactions between proteins and drugs or between proteins), MD simulation is frequently used. MD can help understand molecular structural differences between proteins and small compounds. We used acetylcholinesterase (AChE, PDB ID: 1UT6) to MD chlorogenic and gallic acids, as well as the currently prescribed medication rivastigmine (Standard medication). Furthermore, we determine the binding affinity, which may be responsible for AChE inhibition. MD simulations were performed on docked complexes of chlorogenic acid, gallic acid, and rivastigmine with receptor 1UT6 for a 300 ns trajectory to ensure the stability of docked ligand-protein complexes. Results The results showed that chlorogenic acid has the highest binding affinity and stability for AChE inhibition. In the docking and dynamics analysis, both techniques have predicted chlorogenic acid to be a potential constituent of ACV which shows a similar activity when compared to rivastigmine by virtue of binding affinity. Conclusion These findings identify chlorogenic acid as the key component of ACV that protects against AD-related cognitive and behavioral impairments. This finding will be critical in the development of ACV-based drugs for Alzheimer’s disease treatment.

Novel s-triazine derivatives as potential anticancer agents: Synthesis, DFT, DNA binding, molecular docking, MD simulation and in silico ADMET profiling

The ongoing challenge of cancer in modern medicine highlights the urgent need for targeted therapeutic strategies, particularly against the EGFR/PI3K/AKT/mTOR signalling pathways, which are pivotal in tumorigenesis. This study presents the design, synthesis, characterization, DNA binding studies and computational evaluation of a novel series of trisubstituted s-triazine derivatives 3a–n as potential anticancer agents. The synthetic methodology utilized the reaction of various oxygen-containing nucleophiles with cyanuric chloride via nucleophilic aromatic substitution, yielding the corresponding target products with high yield and purity. Density Functional Theory (DFT) calculations utilizing the B3LYP level provided insights into the electronic properties of the compounds, with derivatives 3f, 3n, and 3l displaying the lowest energy gaps and highest electrophilicity indices, indicative of their enhanced reactivity. DNA binding results from UV–Vis absorption spectroscopy confirmed the groove mode of binding for the most potent compound 3f with the binding constant (Kb) value of 6.75 × 104 M−1. Molecular docking studies against DNA (PDB ID: 3EY0) and EGFR (PDB ID: 6V6O) revealed strong binding affinities, with compound 3f (R1= ethoxy, R2= 3-CF3) exhibiting a notable binding energy of -8.9 kcal/mol and −9.1 kcal/mol respectively. Additionally, these compounds showed significant binding interactions with PI3K (PDB ID: 5HJB) and mTOR (PDB ID: 4JSV), suggesting their potential as dual inhibitors of the PI3K/AKT/mTOR pathway. The drug-likeness and ADMET profiles further support the therapeutic promise of compound 3f bearing a 3-trifluoromethyl substituent.

In silico Evaluation of NO-Sartans against SARS-CoV-2.

Numerous clinical trials are currently investigating the potential of nitric oxide (NO) as an antiviral agent against coronaviruses, including SARS-CoV-2. Additionally, some researchers have reported positive effects of certain Sartans against SARS-CoV-2. Considering the impact of NO-Sartans on the cardiovascular system, we have compiled information on the general structure, synthesis methods, and biological studies of synthesized NOSartans. In silico evaluation of all NO-Sartans and approved sartans against three key SARS-CoV- -2 targets, namely Mpro (PDB ID: 6LU7), NSP16 (PDB ID: 6WKQ), and ACE-2 (PDB ID: 1R4L), was performed using MOE. Almost all NO-Sartans and approved sartans demonstrated promising results in inhibiting these SARS-CoV-2 targets. Compound 36 (CLC-1280) showed the best docking scores against the three evaluated targets and was further evaluated using molecular dynamics (MD) simulations. Based on our in silico studies, CLC-1280 (a Valsartan dinitrate) has the potential to be considered as an inhibitor of the SARS-CoV-2 virus. However, further in vitro and in vivo evaluations are necessary for the drug development process.

Synthesis, In Vivo, ADME Determination, and Molecular Docking Studies of 1,3,4‐Oxadiazoles Containing Pyridine and Piperazine Moieties as New Diuretic Agents

AbstractA series of 1‐(piperazin‐1‐yl)‐2‐((5‐(pyridin‐4‐yl)‐1,3,4‐oxadiazol‐2‐yl)thio)ethan‐1‐one derivatives (9a–l) were prepared using a multistep reaction between 2‐chloro‐1‐(piperazin‐1yl)ethan‐1‐one derivatives (4a–l) and 5‐(pyridine‐4‐yl)‐1,3,4‐oxadiazole‐2‐thiol (8) and studied their diuretic potential by following established in vivo and in silico protocols. The data obtained from the experimental rat animal model in vivo diuretic studies indicated that synthesized derivatives 9d, 9e, 9g, 9i, and 9j possess excellent diuretic potential. The results obtained from in vivo study were also reinforced by the data of in silico studies performed using AutoDock (1.5.7) software. The molecular docking involved interactions of synthesized molecules with two target proteins, that is, human carbonic anhydrase II protein (hCA‐II, PDB ID: 3HS4) and human NKCCl K289NA492E protein (NKCCl, PDB ID: 7S1Y). The ADME properties of the synthesized molecules have also been determined using pkCSM software that established that the synthesized molecules are good candidates for oral absorption. All the data of in vivo and in silico studies synergized the results that state that the diuretic activity of all synthesized compounds is greater than that of the standard drug (furosemide), whereas compounds 9d, 9e, 9g, 9i, and 9j show excellent activity with values of 1.32, 1.33, 1.35, 1.39, and 1.35, respectively.

Enantiomeric C-6 fluorinated swainsonine derivatives as highly selective and potent inhibitors of α-mannosidase and α-l-rhamnosidase: design, synthesis and structure-activity relationship study

Six C-6 fluorinated d-swainsonine derivatives and their enantiomers have been designed based on initial docking calculations, and synthesized from enantiomeric ribose-derived aldehydes, respectively. Glycosidase inhibition assay of these derivatives with d-swainsonine (1) and l-swainsonine (ent-1) as contrasts found that the C-6 fluorinated d-swainsonine derivatives with C-8 configurations as R (α) showed specific and potent inhibitions of jack bean α-mannosidase (model enzyme of Golgi α-mannosidase II); whereas their enantiomers with C-8 configurations as S (β) were powerful and selective α-l-rhamnosidase inhibitors. Molecular docking calculations found the C-6 fluorinatedd-swainsonine derivatives 21, 24 and 25 with highly coincident binding conformations with d-swainsonine (1) in their interactions with the active site of α-mannosidase (PDB ID: 1HWW). Reliability of the docking results were confirmed by Molecular Dynamics (MD) simulation. Additionally, solid interactions with residues Gln-392 and Tyr-393 in the active site of α-l-rhamnosidase (PDB ID: 3W5N) were proved to be vital for potent α-l-rhamnosidase inhibitions of the l-swainsonine derivatives. The role of C-6 fluorines in swainsonine derivatives well demonstrated the “mimic effect” of fluorine to hydrogen by minimal influence on the binding conformations and effective compensation for any possible lost interactions. This work contributes to a comprehensive understanding of the structure-activity relationship (SAR) of the fluorinated swainsonines and ever reported branched swainsonines, and has laid good foundation for development of more potent α-mannosidase and α-l-rhamnosidase inhibitors.

2,2'- Bipyridine Derivatives Exert Anticancer Effects by Inducing Apoptosis in Hepatocellular Carcinoma (HepG2) Cells.

To elucidate the therapeutic potential of 2,2'-bipyridine derivatives [NPS (1-6)] on hepatocellular carcinoma HepG2 cells. The effects on cell survival, colony formation, cellular and nuclear morphology, generation of reactive oxygen species (ROS), change in the integrity of mitochondrial membrane potential (MMP), and apoptosis were investigated. Additionally, docking studies were conducted to analyze and elucidate the interactions between the derivatives and AKT and BRAF proteins. NPS derivatives (1, 2, 5 and 6) significantly impaired cell viability of HepG2 cell lines at nanogram range concentrations - 72.11 ng/mL, 154.42 ng/mL, 71.78 ng/mL, and 71.43 ng/mL, while other derivatives were also effective at concentrations below 1µg/mL. These compounds reduced the colony formation capacity of HepG2 cells in a dose-dependent manner following treatment. Mechanistic studies revealed that these derivatives induce reactive oxygen species (ROS) accumulation and cause mitochondrial membrane depolarization, ultimately triggering apoptosis in HepG2 cells. In the presence of these derivatives, cells demonstrated that 75% of cells underwent apoptosis, compared to 25% in the control group. Additionally, there was a marked increase in mitochondrial depolarization (95% cells) and a threefold rise in ROS levels compared to the controls. Docking studies revealed interactions between the derivatives and the signaling proteins AKT (PDB ID: 6HHF) and BRAF (PDB ID: 8C7Y) with binding affinities ranging from -7.10 to -9.91, highlighting their pivotal role in targeting key players in hepatocellular carcinoma progression. The findings of this study underscore the therapeutic potential of these derivatives against HepG2 cells and offer valuable insights for further experimental validation of their efficacy as inhibitors targeting AKT or BRAF signaling pathways.

Synthesis, spectroscopic characterization, crystallographic studies, Hirshfeld surface analysis, DFT, and molecular docking studies of (4-phenylthiazol-2-yl)(thiophen-2-yl)methanone

In the present research article, we have synthesized a novel (4-phenylthiazol-2-yl)(thiophen-2-yl)methanone molecule. The structure of this compound was confirmed using 1H and 13C NMR spectroscopic techniques. Additionally, the crystal structure was determined through single crystal X-ray diffraction, revealing stabilization by various intra and intermolecular interactions, along with π⋅⋅⋅π interaction. These interactions lead to the formation of R_2^2(4) S(6) and S(5) synthons, which play a crucial role in enhancing the stability of the crystal structure. Moreover, the interactions were verified using Hershfield surface analysis and 2D fingerprint plot evaluations. Energy framework analysis was employed to determine the extent to which the interactions existed and the 3D arrangement of the packing economy within the crystal. The outcomes showed that dispersion energy is higher than repulsion and coulomb energies in the crystal structures' interaction energies and chemical pairs. The electronic properties, such as MEP and HOMO-LUMO energy levels have been investigated using DFT. A substantial HOMO-LUMO energy gap of 3.760 eV suggests that the synthesized molecule exhibits high kinetic stability. Also, molecular docking studies were conducted on the target protein (PDB ID: 3S7S) to explore the binding modes and interactions between the proteins and the ligand.

Phytochemical profiling, spectroscopic identification of active compounds, and mechanism of the anticandidal properties of Datura stramonium L. using SwissADMET prediction and molecular docking analysis

BackgroundDatura stramonium L., a wild-growing herb, has been traditionally used to treat various ailments, including toothache, asthma, rheumatism, epilepsy, and alopecia. Scientific evidence supports its anticancer, anti-inflammatory, anti-asthmatic, anticholinergic, antifungal, and antibacterial properties. AimThis study aimed to isolate, characterize, and identify the most potent anticandidal compounds inhibiting the growth of Candida spp., while also predicting their drug-likeness and toxicity profiles. MethodThe anticandidal activity of D. stramonium leaf extracts was assessed using the Agar well-diffusion method and minimum inhibitory concentration (MIC) was determined by the broth dilution method. The most active extract was selected for column chromatography. Different fractions were collected and screened against pathogenic Candida spp. The most active fraction was subjected to Gas chromatography-Mass spectrometry (GC-MS), Fourier Transform-Infrared Spectroscopy (FT-IR), and Nuclear Magnetic Resonance (NMR) analysis. Additionally, computational tools such as molecular docking and ADMET prediction provided further insights into the molecular interactions between the target enzymes. ResultsIn vitro anticandidal activity demonstrated that the ethyl acetate extract exhibited significant activity against human pathogenic Candida spp., with the highest zones of inhibition against Candida guilliermondii (20.33±0.56 mm), Candida tropicalis (16.33±0.58 mm), and Candida albicans (14.66±1.05 mm), with a minimum inhibitory concentration (MIC) value of 25 ug/ml. Additionally, the most potent fraction (F8) obtained from the Column revealed significant anticandidal activity. GC-MS analysis of the F8 fraction indicated the presence of 23 compounds, with the major compounds being Phthalic acid, di(2-propylpentyl) ester (Compound 1), Pentadecane (Compound 2), Octadecane (Compound 3), Benzoic acid, 3-Amino-5-Hydroxy-, Methyl ester (Compound 4), and 1,2-Benzenedicarboxylic acid, bis (2-ethylhexyl) ester (Compound 5). This study reports all 23 compounds from D. stramonium for the first time. Furthermore, NMR studies confirmed the presence of Phthalic acid, di(2-propylpentyl) ester as the most abundant compound, designated as compound 1. Finally, docking analysis revealed that compound 1 showed good binding affinities for the tested enzymes, with the highest binding scores of -7.084 Kcal/mol and -7.030 Kcal/mol with Lanosterol 14-alpha demethylase (PDB ID: 5JLC, 5TZ1). The results of the in silico pharmacokinetic and drug-likeness properties indicated that compound 1 is a potential anticandidal drug candidate. ConclusionThis study highlights that 23 compounds were reported from the leaf extract of D. stramonium for the first time. The findings suggest that compound 1 can be considered a new anticandidal drug candidate.

Screening and identification of phytochemicals from Acorus calamus L. to overcome NDM-1 mediated resistance in Klebsiella pneumoniae using in silico approach

Klebsiella pneumoniae is a potent human pathogen and a prevalent ESKAPE (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species). Considerably, K. pneumoniae becomes a major clinical problem due to numerous AMR genes [extended-spectrum β-lactamase, plasmid-mediated AmpC, carbapenemases, tigecycline resistance, and New Delhi Metallo-β-lactamase-1 (NDM-1)] and can hydrolyse the majority of β-lactam antibiotics. Hence, targeting NDM-1 could be an effective approach to eradicate K. pneumoniae pathogenesis. A plethora of reports suggests that the plant compounds possess an anti-microbial activity and their utilization could be a promising strategy to develop novel antibiotics. Our study utilized the hydromethanolic leaves extract of Acorus calamus L. (AC) to target NDM-1 containing K. pneumonia using an in silico approach. At first, we determined the phytochemical composition of AC using GC-HRMS. Further, the phytoconstituents were screened against the NDM-1 (PDB ID: 3ZR9) of K. pneumoniae through molecular docking studies. Our results revealed the compounds from AC such as [(2R,4S,6R,7S,8R,9S,13S)-16-hydroxy-5’,7,9,13-tetramethylspiro[5-oxapentacyclo[10.8.0.02,9.04,8.013,18]icos-1(12)-ene-6,2’-oxane]-11-one (-9.5 kcal/mol), 4,4,5,8-tetramethyl-2,3-dihydrochromen-2-ol (-6.6 kcal/mol), 5-chloro-2-(2,4-dichloro phenoxy)phenol (-6.0 kcal/mol), [(3S,3aS,6R,6aS)-3-nitrooxy-2,3,3a,5,6,6a-hexahydrofuro[3,2-b]furan-6-yl] nitrate (-5.7 kcal/mol), 4-(3-hydroxyprop-1-enyl)-2-methoxyphenol (-5.6 kcal/mol), and (E)-3-(2,4-dimethoxyphenyl)prop-2-enoic acid (-5.6 kcal/mol)] possess substantial docking scores against NDM-1. Therefore, our study concludes that phytochemicals of AC may inhibit NDM-1-mediated resistance in K. pneumoniae and could be an alternative therapeutic strategy for targeting NDM-1-containing K. pneumoniae.